Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification

• Published in: Journal of nanobiotechnology Vol. 20; no. 1; pp. 1 - 334
• Main Authors: Guo, Bei, Shan, Su-Kang, Xu, Feng, Lin, Xiao, Li, Fu-Xing-zi, Wang, Yi, Xu, Qiu-Shuang, Zheng, Ming-Hui, Lei, Li-Min, Li, Chang-Chun, Zhou, Zhi-Ang, Ullah, Muhammad Hasnain Ehsan, Wu, Feng, Liao, Xiao-Bo, Yuan, Ling-Qing
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 16.07.2022; BioMed Central; BMC
• Subjects: Advanced glycosylation end products; Apoptosis; Biomedical materials; Calcification; Calcification (ectopic); Care and treatment; Cell differentiation; Complications and side effects; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Differentiation (biology); Endothelial cells; Endothelium; Experiments; Extracellular vesicles; Glycosylation; Health aspects; miR-126-5p; miRNA; Muscles; Nanoparticles; Pathogenesis; Proteins; sEVs; Signal transduction; Smooth muscle; Software; Transmission electron microscopy; Umbilical vein; Vascular calcification; Vesicles; China; United Kingdom > UK; United States > US
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01529-z

The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo.